Geum-Sook Hwang

Metabolomic studies on geographical grapes and their wines using 1H NMR analysis coupled with multivariate statistics.

Environmental vineyard conditions can affect the chemical composition or metabolites of grapes and their wines. Grapes grown in three different regions of South Korea were collected and separated into pulp, skin, and seed. The grapes were also vinified after crushing. (1)H NMR spectroscopy with pattern recognition (PR) methods was used to investigate the metabolic differences in pulp, skin, seed, and wines from the different regions. Discriminatory compounds among the grapes were Na, Ca, K, malate, citrate, threonine, alanine, proline, and trigonelline according to PR methods of principal component analysis (PCA) or partial least-squares discriminant analysis (PLS-DA). Grapes grown in regions with high sun exposure and low rainfall showed higher levels of sugar, proline, Na, and Ca together with lower levels of malate, citrate, alanine, threonine, and trigonelline than those grown in regions with relatively low sun exposure and high rainfall. Environmental effects were also observed in the complementary wines. This study demonstrates that (1)H NMR-based metabolomics coupled with multivariate statistical data sets can be useful for determining grape and wine quality.

1H-NMR-based metabolomics study of cerebral infarction.

Background and Purpose— Stroke is one of the leading causes of adult disability and death in developing countries. However, early diagnosis is difficult and no reliable biomarker is currently available. Thus, we applied a 1H-NMR metabolomics approach to investigate the altered metabolic pattern in plasma and urine from patients with cerebral infarctions and sought to identify metabolic biomarkers associated with stroke. Methods— Metabolic profiles of plasma and urine from patients with cerebral infarctions, especially small vessel occlusion, were investigated using 1H-NMR spectroscopy coupled with multivariate statistical analysis, such as principal components analysis and orthogonal partial least-squares discriminant analysis. Results— Multivariate statistical analysis showed a significant separation between patients and healthy individuals. The plasma of stroke patients was characterized by the increased excretion of lactate, pyruvate, glycolate, and formate, and by the decreased excretion of glutamine and methanol; the urine of stroke patients was characterized by decreased levels of citrate, hippurate, and glycine. These metabolites detected from plasma and urine of patients with cerebral infarctions were associated with anaerobic glycolysis, folic acid deficiency, and hyperhomocysteinemia. Furthermore, the presence of cerebral infarction in the external validation model was predicted with high accuracy. Conclusions— These data demonstrate that a metabolomics approach may be useful for the effective diagnosis of cerebral infarction and for the further understanding of stroke pathogenesis.

(1)H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis.

Tuberculosis (TB) is one of three major infectious diseases, and the control of TB is becoming more difficult because of the emergence of multidrug-resistant and extensively drug-resistant strains. In this study, we explored the (1)H NMR-based metabolomics of TB using an aerobic TB infection model. Global profiling was applied to characterize the responses of C57Bl/6 mice to an aerobic infection with virulent Mycobacterium tuberculosis (MTB). The metabolic changes in organs (i.e., the lung, the target organ of TB, and the spleen and liver, remote systemic organs) and in serum from control and MTB-infected rats were investigated to clarify the host-pathogen interactions in MTB-infected host systems. Principal components analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots showed distinct separation between control and MTB-infected rats for all tissue and serum samples. Several tissue and serum metabolites were changed in MTB-infected rats, as compared to control rats. The precursors of membrane phospholipids, phosphocholine, and phosphoethanolamine, as well as glycolysis, amino acid metabolism, nucleotide metabolism, and the antioxidative stress response were altered based on the presence of MTB infection. This study suggests that NMR-based global metabolite profiling of organ tissues and serum could provide insight into the metabolic changes in host infected aerobically with virulent Mycobacterium tuberculosis.

1H Nuclear Magnetic Resonance-Based Metabolomic Characterization of Wines by Grape Varieties and Production Areas

(1)H NMR spectroscopy was used to investigate the metabolic differences in wines produced from different grape varieties and different regions. A significant separation among wines from Campbell Early, Cabernet Sauvignon, and Shiraz grapes was observed using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The metabolites contributing to the separation were assigned to be 2,3-butanediol, lactate, acetate, proline, succinate, malate, glycerol, tartarate, glucose, and phenolic compounds by PCA and PLS-DA loading plots. Wines produced from Cabernet Sauvignon grapes harvested in the continental areas of Australia, France, and California were also separated. PLS-DA loading plots revealed that the level of proline in Californian Cabernet Sauvignon wines was higher than that in Australian and French Cabernet Sauvignon, Australian Shiraz, and Korean Campbell Early wines, showing that the chemical composition of the grape berries varies with the variety and growing area. This study highlights the applicability of NMR-based metabolomics with multivariate statistical data sets in determining wine quality and product origin.

Oxazaborolidinium Ion-Catalyzed Cyclopropanation of α-Substituted Acroleins: Enantioselective Synthesis of Cyclopropanes Bearing Two Chiral Quaternary Centers

A catalytic synthetic route to highly functionalized chiral cyclopropane derivatives was developed by Michael-initiated cyclopropanation of α-substituted acroleins with aryl- and alkyl diazoacetates. In the presence of chiral (S)-oxazaborolidinium cation 1b as a catalyst, the reaction proceeded in high yield (up to 93%) with high to excellent diastereoselectivity (up to 98% de) and enantioselectivity (up to 95% ee).

Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis

Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify the pathogenesis of asthma by systemic review.

1H NMR-based metabolomic approach for understanding the fermentation behaviors of wine yeast strains.

(1)H NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to investigate metabolic changes in musts during alcoholic fermentation and wines during aging. Three Saccharomyces cerevisiae yeast strains (RC-212, KIV-1116, and KUBY-501) were also evaluated for their impacts on the metabolic changes in must and wine. Pattern recognition (PR) methods, including PCA, PLS-DA, and OPLS-DA scores plots, showed clear differences for metabolites among musts or wines for each fermentation stage up to 6 months. Metabolites responsible for the differentiation were identified as valine, 2,3-butanediol (2,3-BD), pyruvate, succinate, proline, citrate, glycerol, malate, tartarate, glucose, N-methylnicotinic acid (NMNA), and polyphenol compounds. PCA scores plots showed continuous movements away from days 1 to 8 in all musts for all yeast strains, indicating continuous and active fermentation. During alcoholic fermentation, the highest levels of 2,3-BD, succinate, and glycerol were found in musts with the KIV-1116 strain, which showed the fastest fermentation or highest fermentative activity of the three strains, whereas the KUBY-501 strain showed the slowest fermentative activity. This study highlights the applicability of NMR-based metabolomics for monitoring wine fermentation and evaluating the fermentative characteristics of yeast strains.

Evidence of vintage effects on grape wines using 1H NMR-based metabolomic study.

The chemical composition of grape wines varies with grape variety, environmental factors of climate and soil, and bacterial strains, which can each affect the wine quality. Using (1)H NMR analysis coupled with multivariate statistical data sets, we investigated the effects of grape vintage on metabolic profiles of wine and the relationship between wine metabolites and meteorological data. Principal component analysis (PCA) showed a clear differentiation between Meoru wines that were vinified with the same yeast strain and Meoru grapes harvested from the same vineyard but with a different vintage. The metabolites contributing to the differentiation were identified as 2,3-butandiol, lactic acid, alanine, proline, gamma-aminobutyric acid (GABA), choline, and polyphenols, by complementary PCA loading plot. Markedly higher levels of proline, lactic acid and polyphenols were observed in the 2006 vintage wines compared to those of 2007 vintage, showing excellent agreement with the meteorological data that the sun-exposed time and rainfall in 2006 were approximately two times more and four times less, respectively, than those in 2007. These results revealed the important role of climate during ripening period in the chemical compositions of the grape. This study highlights the reliability of NMR-based metabolomic data by integration with meteorological data in characterizing wine or grape.

Enantioselective Synthesis of β-Iodo Morita–Baylis–Hillman Esters by a Catalytic Asymmetric Three-Component Coupling Reaction†

A catalytic route toward chiral Morita-Baylis-Hillman esters by asymmetric coupling between alpha,beta-acetylenic esters, aldehydes, and trimethylsilyl iodide has been developed (see scheme). The reaction proceeds with high to excellent enantioselectivities, and the products can be transformed into beta-branched derivatives in a single step and with excellent retention of configuration. TMS = trimethylsilyl.

Dialysis modality-dependent changes in serum metabolites: accumulation of inosine and hypoxanthine in patients on haemodialysis

BACKGROUND The body metabolism of patients with end-stage renal disease may be altered in response to long-term dialysis treatment. Moreover, the pattern of serum metabolites could change depending on the type of dialysis modality used. However, dialysis modality-dependent changes in serum metabolites are poorly understood. Our aim was to profile comprehensively serum metabolites by exploiting a novel method of (1)H-NMR-based metabonomics and identify the differences in metabolite patterns in subjects receiving haemodialysis (HD) and peritoneal dialysis (PD). METHODS Anuric and non-diabetic HD patients were matched to PD patients for age, sex and dialysis duration. Accurate concentrations of serum metabolites were determined using the target-profiling procedure, and differences in the levels of metabolites were compared using multivariate analysis. RESULTS Principal Components Analysis score plots showed that the metabolic patterns could be discriminated by dialysis modalities. Hypoxanthine and inosine were present only with HD, whereas serum xanthine oxidase activity and uric acid levels were not different. In contrast, PD was associated with higher levels of lactate, glucose, maltose, pyruvate, succinate, alanine, and glutamate linked to glucose metabolism and the tri-carboxylic acid cycle. Maltose appeared only in patients using icodextrin solution for PD. Known uraemic retention solutes such as urea, creatinine, myo-inositol and trimethylamine-N-oxide were increased in both dialysis groups. CONCLUSIONS Metabonomics shows apparent differences in the profiles of serum metabolites between HD and PD, which were influenced by dialysis-related processes. Inosine and hypoxanthine are present only in HD patients, which is likely to represent more hypoxic and oxidative stress.